Malonic Acid → (+/-)-3-(4-Chlorophenyl)-8-azabicyclo[3.2.1]oct-2-ene malonate

Participants

Reaction Steps

To a stirred solution of 3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene (2 g, 8.5 mmol) in anhydrous 1,2-dichloroethane (20 ml) under nitrogen atmosphere 1-chloroethyl chloroformate (1.25 ml, 11.6 mmol) was added. The reaction mixture was heated at reflux overnight, then 1-chloroethyl chloroformate (1 ml, 9.3 mmol) was added and once again the reaction mixture was heated at reflux overnight. The reaction mixture was concentrated to an oil and the oil was dissolved in methanol (25 ml). This solution was heated at reflux for 2 hours and then concentrated to an oil. The residue was dissolved in water and concentrated NH4OH was added until pH 10 was reached. The water phase was extracted with diethyl ether. The organic phase was dried with magnesium sulphate and concentrated to dryness. The residue was chromatographed over silica gel (dichloromethane/ace-tone/methanol, 4/1/1 (v/v)). The product fractions were concentrated to an oil, the oil was dissolved in ethanol (96%) and malonic acid (0.55 g, 5.3 mmol) in ethanol (96%) was added. This solution was concentrated to an oil, the oil was triturated in diethyl ether. The title compound precipitated as a powder and was isolated by filtration. Yield (1.32 g, 48%), m.p. 136.1-138° C.

Provenance & Evidence